EP0033981A3 - Preparation of bridged catharanthus alkaloid dimers - Google Patents
Preparation of bridged catharanthus alkaloid dimers Download PDFInfo
- Publication number
- EP0033981A3 EP0033981A3 EP81101924A EP81101924A EP0033981A3 EP 0033981 A3 EP0033981 A3 EP 0033981A3 EP 81101924 A EP81101924 A EP 81101924A EP 81101924 A EP81101924 A EP 81101924A EP 0033981 A3 EP0033981 A3 EP 0033981A3
- Authority
- EP
- European Patent Office
- Prior art keywords
- bridged
- preparation
- formula
- catharanthus alkaloid
- dimers
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D519/04—Dimeric indole alkaloids, e.g. vincaleucoblastine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
A novel process for preparing a compound of the
formula
R⁶-NH-CH₂-(CH₂)n-Q-(CH₂)nCH₂-NH-R⁶ (I)
is described wherein each R⁶ is the residue of an indole dihydroindole alkaloid of the formula wherein
R² is CH₃ or H;
when taken singly, one of R³ and R⁴ is OH or H and the other is C₂H₅ and R⁵ is H; and when R⁴ and R⁵ are taken together, they form an α-epoxide ring and R³ is C₂H₅;
Q is S-S and each n is 0, 1, 2, 3, 4 which comprises reacting an azide of the formula R⁶-N₃ with a diamine of the formula
NH₂-CH₂-(CH₂)n-Q-(CH₂)n-CH₂-NH₂
in the ratio of two moles of R⁶-N₃ per mole of diamine.
R⁶-NH-CH₂-(CH₂)n-Q-(CH₂)nCH₂-NH-R⁶ (I)
is described wherein each R⁶ is the residue of an indole dihydroindole alkaloid of the formula wherein
R² is CH₃ or H;
when taken singly, one of R³ and R⁴ is OH or H and the other is C₂H₅ and R⁵ is H; and when R⁴ and R⁵ are taken together, they form an α-epoxide ring and R³ is C₂H₅;
Q is S-S and each n is 0, 1, 2, 3, 4 which comprises reacting an azide of the formula R⁶-N₃ with a diamine of the formula
NH₂-CH₂-(CH₂)n-Q-(CH₂)n-CH₂-NH₂
in the ratio of two moles of R⁶-N₃ per mole of diamine.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/905,667 US4199504A (en) | 1978-05-15 | 1978-05-15 | Bridged cathranthus alkaloid dimers |
| US905667 | 1978-05-15 |
Related Parent Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP79300826A Division EP0005620A1 (en) | 1978-05-15 | 1979-05-14 | Bridged catharanthus alkaloid dimers, their preparation and formulations containing them |
| EP79300826.9 Division | 1979-05-14 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP0033981A2 EP0033981A2 (en) | 1981-08-19 |
| EP0033981A3 true EP0033981A3 (en) | 1981-09-09 |
Family
ID=25421234
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP81101927A Withdrawn EP0032756A3 (en) | 1978-05-15 | 1979-05-14 | Intermediates used in the preparation of bridged catharanthus alkaloid dimers |
| EP79300826A Withdrawn EP0005620A1 (en) | 1978-05-15 | 1979-05-14 | Bridged catharanthus alkaloid dimers, their preparation and formulations containing them |
| EP81101924A Withdrawn EP0033981A3 (en) | 1978-05-15 | 1979-05-14 | Preparation of bridged catharanthus alkaloid dimers |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP81101927A Withdrawn EP0032756A3 (en) | 1978-05-15 | 1979-05-14 | Intermediates used in the preparation of bridged catharanthus alkaloid dimers |
| EP79300826A Withdrawn EP0005620A1 (en) | 1978-05-15 | 1979-05-14 | Bridged catharanthus alkaloid dimers, their preparation and formulations containing them |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US4199504A (en) |
| EP (3) | EP0032756A3 (en) |
| JP (1) | JPS54148798A (en) |
| AU (1) | AU4691379A (en) |
| BE (1) | BE876155A (en) |
| CA (1) | CA1114816A (en) |
| CS (1) | CS214792B2 (en) |
| DD (3) | DD147543A5 (en) |
| DK (1) | DK197579A (en) |
| ES (3) | ES480560A1 (en) |
| FI (1) | FI791519A (en) |
| FR (2) | FR2435480A1 (en) |
| GB (1) | GB2022080A (en) |
| GR (1) | GR73047B (en) |
| IL (1) | IL57434A0 (en) |
| LU (1) | LU81254A1 (en) |
| PH (3) | PH14999A (en) |
| PL (2) | PL120896B1 (en) |
| PT (1) | PT69589A (en) |
| RO (1) | RO81682B (en) |
| ZA (1) | ZA792271B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4362664A (en) * | 1980-12-29 | 1982-12-07 | Eli Lilly And Company | Vinblastine oxazolidinedione disulfides and related compounds |
| EP0123441B1 (en) * | 1983-03-30 | 1990-10-03 | Lilly Industries Limited | Vincaleukoblastine derivatives |
| WO2000006582A1 (en) * | 1998-07-31 | 2000-02-10 | Goldsmith Seeds, Inc. | Trimeric and polymeric alkaloids |
| EP2289549A3 (en) | 1999-10-01 | 2011-06-15 | Immunogen, Inc. | Immunoconjugates for treating cancer |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2297043A1 (en) * | 1975-01-09 | 1976-08-06 | Lilly Co Eli | NEW AMID DERIVATIVES OF VINBLASTINE, LEUROSIDINE, LEUROCRISTINE AND RELATED DIMERAL ALKALOIDS |
| GB1463575A (en) * | 1973-04-02 | 1977-02-02 | Lilly Co Eli | Vinca alkaloid derivatives |
| DE2739443A1 (en) * | 1976-09-08 | 1978-03-09 | Lilly Co Eli | DIMERE INDOL-DIHYDROINDOLCARBOXAMIDES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE |
| FR2400029A1 (en) * | 1977-08-08 | 1979-03-09 | Lilly Co Eli | Amide derivs. of leurosine and leuroformine and de:acetyl analogues - and carbo:azide precursors, useful as antitumour agents |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4115388A (en) * | 1977-03-30 | 1978-09-19 | Eli Lilly And Company | 3'-Oxygenated derivatives of 4'-deoxy VLB "A" and "B" and related 1-formyl compounds |
-
1978
- 1978-05-15 US US05/905,667 patent/US4199504A/en not_active Expired - Lifetime
-
1979
- 1979-05-05 PH PH22464A patent/PH14999A/en unknown
- 1979-05-08 PT PT69589A patent/PT69589A/en unknown
- 1979-05-09 AU AU46913/79A patent/AU4691379A/en not_active Abandoned
- 1979-05-10 FR FR7911882A patent/FR2435480A1/en active Pending
- 1979-05-10 BE BE1/9386A patent/BE876155A/en unknown
- 1979-05-10 ZA ZA792271A patent/ZA792271B/en unknown
- 1979-05-10 CA CA327,351A patent/CA1114816A/en not_active Expired
- 1979-05-11 FI FI791519A patent/FI791519A/en not_active Application Discontinuation
- 1979-05-12 GR GR59071A patent/GR73047B/el unknown
- 1979-05-14 LU LU81254A patent/LU81254A1/en unknown
- 1979-05-14 DK DK197579A patent/DK197579A/en unknown
- 1979-05-14 EP EP81101927A patent/EP0032756A3/en not_active Withdrawn
- 1979-05-14 EP EP79300826A patent/EP0005620A1/en not_active Withdrawn
- 1979-05-14 EP EP81101924A patent/EP0033981A3/en not_active Withdrawn
- 1979-05-14 ES ES480560A patent/ES480560A1/en not_active Expired
- 1979-05-14 JP JP5962979A patent/JPS54148798A/en active Pending
- 1979-05-14 CS CS793284A patent/CS214792B2/en unknown
- 1979-05-14 ES ES480562A patent/ES480562A1/en not_active Expired
- 1979-05-14 ES ES480561A patent/ES480561A1/en not_active Expired
- 1979-05-14 GB GB7916702A patent/GB2022080A/en not_active Withdrawn
- 1979-05-14 RO RO97514A patent/RO81682B/en unknown
- 1979-05-15 PL PL1979222094A patent/PL120896B1/en unknown
- 1979-05-15 DD DD79217285A patent/DD147543A5/en unknown
- 1979-05-15 DD DD79217286A patent/DD150467A5/en unknown
- 1979-05-15 PL PL21559379A patent/PL215593A1/xx unknown
- 1979-05-15 DD DD79212894A patent/DD143618A5/en unknown
- 1979-05-30 IL IL57434A patent/IL57434A0/en unknown
- 1979-10-31 FR FR7926971A patent/FR2438052A1/en active Pending
-
1980
- 1980-03-06 PH PH23731A patent/PH14904A/en unknown
- 1980-03-06 PH PH23730A patent/PH14907A/en unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1463575A (en) * | 1973-04-02 | 1977-02-02 | Lilly Co Eli | Vinca alkaloid derivatives |
| FR2297043A1 (en) * | 1975-01-09 | 1976-08-06 | Lilly Co Eli | NEW AMID DERIVATIVES OF VINBLASTINE, LEUROSIDINE, LEUROCRISTINE AND RELATED DIMERAL ALKALOIDS |
| DE2739443A1 (en) * | 1976-09-08 | 1978-03-09 | Lilly Co Eli | DIMERE INDOL-DIHYDROINDOLCARBOXAMIDES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE |
| FR2400029A1 (en) * | 1977-08-08 | 1979-03-09 | Lilly Co Eli | Amide derivs. of leurosine and leuroformine and de:acetyl analogues - and carbo:azide precursors, useful as antitumour agents |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0032756A3 (en) | 1981-09-09 |
| PH14907A (en) | 1982-01-29 |
| JPS54148798A (en) | 1979-11-21 |
| GB2022080A (en) | 1979-12-12 |
| RO81682B (en) | 1983-04-30 |
| CA1114816A (en) | 1981-12-22 |
| PL222094A1 (en) | 1980-10-20 |
| PL215593A1 (en) | 1980-06-16 |
| FI791519A (en) | 1979-11-16 |
| AU4691379A (en) | 1979-11-22 |
| IL57434A0 (en) | 1979-09-30 |
| DK197579A (en) | 1979-11-16 |
| DD150467A5 (en) | 1981-09-02 |
| ES480560A1 (en) | 1980-04-01 |
| PH14999A (en) | 1982-03-22 |
| EP0033981A2 (en) | 1981-08-19 |
| CS214792B2 (en) | 1982-05-28 |
| PL120896B1 (en) | 1982-03-31 |
| RO81682A (en) | 1983-04-29 |
| BE876155A (en) | 1979-11-12 |
| EP0032756A2 (en) | 1981-07-29 |
| FR2438052A1 (en) | 1980-04-30 |
| US4199504A (en) | 1980-04-22 |
| ES480561A1 (en) | 1980-04-01 |
| DD147543A5 (en) | 1981-04-08 |
| PH14904A (en) | 1982-01-29 |
| EP0005620A1 (en) | 1979-11-28 |
| ZA792271B (en) | 1980-12-31 |
| FR2435480A1 (en) | 1980-04-04 |
| GR73047B (en) | 1984-01-26 |
| LU81254A1 (en) | 1979-09-10 |
| ES480562A1 (en) | 1980-04-01 |
| PT69589A (en) | 1979-06-01 |
| DD143618A5 (en) | 1980-09-03 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| PUAL | Search report despatched |
Free format text: ORIGINAL CODE: 0009013 |
|
| 17P | Request for examination filed |
Effective date: 19810316 |
|
| AC | Divisional application: reference to earlier application |
Ref document number: 5620 Country of ref document: EP |
|
| AK | Designated contracting states |
Designated state(s): DE GB IT NL SE |
|
| AK | Designated contracting states |
Designated state(s): DE GB IT NL SE |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN |
|
| 18W | Application withdrawn |
Withdrawal date: 19820208 |
|
| RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: GERZON, KOERT Inventor name: CONRAD, ROBERT ALLEN |